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1: Am J Kidney Dis 1996 May;27(5):647-51 Related
Articles, Books, LinkOut We retrospectively evaluated the prevalence of primary glomerular lesions in adults who had a renal biopsy for nephrotic proteinuria. From July 1975 to May 1994, 340 patients undergoing renal biopsies evaluated at Rush-Presbyterian-St Lukes Medical Center had the primary glomerular lesions of minimal-change disease, focal segmental glomerular sclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephropathy, immunoglobulin A nephropathy, and immunotactoid glomerulopathy. The patients had a mean age of 43 +/- 17 years, 57% were male, and 50% were white, 36% were black, 7% were of other race, and 7% were of unknown race. The distribution of lesions for black patients was minimal-change disease 14%, FSGS 57%, MGN 24%, membranoproliferative glomerulonephritis 2%, immunoglobulin A 2%, and immunotactoid glomerulopathy 1%; for white patients, the distribution of lesions was minimal-change disease 20%, FSGS 23%, MGN 36%, membranoproliferative glomerulonephropathy 6%, immunoglobulin A 8%, and immunotactoid glomerulopathy 6%. The prevalence of FSGS was significantly greater (P < 0.0001) and that for MGN, immunoglobulin A, and immunotactoid glomerulopathy was significantly less (P < 0.05) for black patients compared with white patients. In a logistic regression analysis, race remained the only significant predictor of FSGS (P = 0.0001), with black patients four times as likely to have FSGS as white patients. The distribution of lesions among white patients was similar based on gender, age, and biopsy period. For black patients the distribution was also similar based on gender and age, but over 20 years the incidence of FSGS increased from 39% (1975 to 1984) to 64% (1985 to 1994) (P < 0.01). Thus, significant racial differences in the distribution of primary glomerular lesions exists. This has important prognostic and therapeutic implications for nephrotic adults. |
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Am J Kidney Dis 2000 May;35(5):878-83 Related Articles,
Books, LinkOut Studies performed at large metropolitan medical centers have reported an increasing incidence of idiopathic focal segmental glomerulosclerosis (FSGS) in adults. To determine whether a similar trend occurs in small urban and rural communities and to determine the role of race in these observations, we reviewed the patient records of all adults who underwent renal biopsies at our institution over the 20-year period from 1974 to 1994. The patients were grouped for analysis in 5-year intervals, 1975 to 1979, 1980 to 1984, 1985 to 1989, and 1990 to 1994, for the following diagnoses: FSGS, membranous nephropathy (MN), minimal change nephropathy (MCN), membranoproliferative glomerulonephritis (MPGN), immunoglobulin A (IgA) nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, and chronic interstitial nephritis. Patients with secondary causes for these lesions were excluded. The relative frequency of FSGS increased from 13.7% during 1975 to 1979 to 25% during 1990 to 1994 (P < 0.05). The relative frequency of MN decreased from 38.3% during 1975 to 1979 to 14.5% during 1990 to 1994 (P < 0.01). There were no changes in the frequencies of MCN, MPGN, IgA nephropathy, chronic glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, or chronic interstitial nephritis over the 20-year period. However, there was a significant increase in the percentage of blacks with FSGS, from 0% in 1975 to 1979 to 22.6% in 1990 to 1994, and an increased percentage of Hispanics with FSGS, from 0% in 1975 to 1979 to 21.3% in 1990 to 1994 (P < 0.05). The modest increase in whites with FSGS did not reach statistical significance. The incidence of MN in blacks and whites decreased over the 20-year period. In the last 5 years, 15 patients per year had FSGS compared with 7 patients per year with MN (P < 0.05). No changes in age or sex between groups or over time accounted for these results. We conclude that FSGS is now diagnosed twice as often as MN and is the most common idiopathic glomerular disease at our hospital. Reasons for this increase include the emergence of FSGS in both Hispanics and blacks, with a modest increase of FSGS in whites. The increase in FSGS in the three most common races in our community suggests that factors other than genetic, perhaps environmental, have a role in the pathogenesis of FSGS. |
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Laurinavicius A, Hurwitz S, Rennke HG. Collapsing
glomerulopathy in HIV and non-HIV patients: a
clinicopathological and follow-up study. Kidney Int 1999
Dec;56(6):2203-13 Related Articles, Books, LinkOut Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. BACKGROUND: Collapsing glomerulopathy (CG) is a pattern of renal injury that is seen in association with HIV infection and that is increasingly recognized in non-HIV patients. METHODS: A review of native kidney biopsies with CG that were diagnosed between 1979 and 1997 in 18 HIV and 42 non-HIV patients is provided. RESULTS: HIV and non-HIV patients with CG were similar in terms of age, sex ratio, serum creatinine, proteinuria, the extent of collapsing and sclerosing glomerular lesions, and interstitial damage. A slight female predominance was found in both groups. In contrast to non-HIV patients, the HIV group was characterized by a high prevalence of blacks (94 vs. 57%), frequent tubuloreticular inclusions (76 vs. 29%), and microcystic tubular changes (72 vs. 40%). In 13 non-HIV patients, CG was associated with a systemic lupus erythematosus (SLE)-like disease (5), hepatitis C virus (HCV) infection (3), HTLV-I infection, MCTD, acute monoblastic leukemia, multiple myeloma, and cerebral arteritis. Overall, the renal survival of human immunodeficiency virus (HIV) and non-HIV patients with CG was not significantly different. Cox regression revealed that HIV infection had an adverse effect on short-term renal survival, with other significant risk factors being extensive interstitial fibrosis, high serum creatinine, proteinuria, and a low percentage of glomeruli with collapse. The slope of reciprocal creatinine was best predicted by the degree of proteinuria. Serum creatinine correlated with the extent of interstitial fibrosis, the male gender, and the percentage of glomeruli with collapse. Proteinuria was best predicted by the extent of effacement of podocyte foot processes. CONCLUSIONS: CG shares many clinicopathological similarities in HIV and non-HIV patients. In some non-HIV patients, CG was associated with autoimmune diseases, lymphoproliferative disorders, and viral infections. |
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Cheng JT, Anderson HL Jr, Markowitz GS, Appel GB, Pogue
VA, D'Agati VD. Hepatitis C virus-associated glomerular
disease in patients with human immunodeficiency virus
coinfection. J Am Soc Nephrol 1999 Jul;10(7):1566-74 Related
Articles, Books, LinkOut Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy.
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Pediatr Nephrol 2000 Feb;14(2):132-7 Related Articles,
Books, LinkOut Idiopathic collapsing glomerulopathy (ICG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis, characterized clinically by rapid progression of renal insufficiency, a male and African-American racial predominance, and pathologically by segmental glomerular collapse, visceral epithelial cell hypertrophy and hyperplasia, and the absence of endothelial tubuloreticular inclusions. Pathologically similar lesions have been reported in adult and pediatric patients with human immunodeficiency virus (HIV) infection and/or intravenous (IV) drug abuse. Most patients with ICG who have been reported in the literature are adults. Six children with ICG were retrospectively identified (two from East Carolina University, four from University of North Carolina-Chapel Hill). Clinical data and renal biopsy findings were reviewed for all patients. All six patients were male; five African-American and one Hispanic. Ages ranged from 2 to 17 years (mean 12 years). Steroid-resistant nephrotic syndrome was the presenting clinical finding. Average 24-h urine protein excretion was 6.3 g (range 3.2-15 g). Five patients were serologically negative for HIV infection (one patient not tested) and none had a history of IV drug abuse or known HIV risk factors. Progression to end-stage renal insufficiency in two patients within 1 year of biopsy required renal transplantation, and within 1 month of biopsy one patient required dialysis. We report a series of pediatric patients with ICG, an aggressive variant of focal segmental glomerulosclerosis. ICG in children is similar clinically and pathologically to this disease in adult patients. |
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Laurinavicius A, Hurwitz S, Rennke HG Collapsing
glomerulopathy in HIV and non-HIV patients: a
clinicopathological and follow-up study. Kidney Int 1999
Dec;56(6):2203-13 Related Articles, Books, LinkOut Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. BACKGROUND: Collapsing glomerulopathy (CG) is a pattern of renal injury that is seen in association with HIV infection and that is increasingly recognized in non-HIV patients. METHODS: A review of native kidney biopsies with CG that were diagnosed between 1979 and 1997 in 18 HIV and 42 non-HIV patients is provided. RESULTS: HIV and non-HIV patients with CG were similar in terms of age, sex ratio, serum creatinine, proteinuria, the extent of collapsing and sclerosing glomerular lesions, and interstitial damage. A slight female predominance was found in both groups. In contrast to non-HIV patients, the HIV group was characterized by a high prevalence of blacks (94 vs. 57%), frequent tubuloreticular inclusions (76 vs. 29%), and microcystic tubular changes (72 vs. 40%). In 13 non-HIV patients, CG was associated with a systemic lupus erythematosus (SLE)-like disease (5), hepatitis C virus (HCV) infection (3), HTLV-I infection, MCTD, acute monoblastic leukemia, multiple myeloma, and cerebral arteritis. Overall, the renal survival of human immunodeficiency virus (HIV) and non-HIV patients with CG was not significantly different. Cox regression revealed that HIV infection had an adverse effect on short-term renal survival, with other significant risk factors being extensive interstitial fibrosis, high serum creatinine, proteinuria, and a low percentage of glomeruli with collapse. The slope of reciprocal creatinine was best predicted by the degree of proteinuria. Serum creatinine correlated with the extent of interstitial fibrosis, the male gender, and the percentage of glomeruli with collapse. Proteinuria was best predicted by the extent of effacement of podocyte foot processes. CONCLUSIONS: CG shares many clinicopathological similarities in HIV and non-HIV patients. In some non-HIV patients, CG was associated with autoimmune diseases, lymphoproliferative disorders, and viral infections.
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Grcevska L, Polenakovik M. Collapsing glomerulopathy:
clinical characteristics and follow-up. Am J Kidney Dis 1999
Apr;33(4):652-7 In 1986, Weiss et al reported a group of patients with nephrotic syndrome, progressive chronic renal failure, and the histopathologic features of glomerular capillary collapse. Similar lesions are often described in human immunodeficiency virus (HIV) nephropathy. We evaluated 893 consecutive nontransplant renal biopsies performed in our department and the follow-up of the patients at our outpatient service. Sixteen specimens were identified with the pathological features of collapsing glomerulopathy (focal segmental or global glomerular capillary collapse and visceral epithelial cell hyperplasia), with no evidence of HIV infection and/or intravenous drug abuse. Their clinical characteristics were analyzed and compared with a group of 29 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). The follow-up period of both patient groups was 5 +/- 1.46 years. The Kaplan-Meier life table method was used to present survival of the patients. The age of both groups was similar, 34 +/- 4 years (mean +/- standard error of the mean) for patients with collapsing glomerulopathy and 35 +/- 3 years for those with FSGS. The serum creatinine level was greater in patients with collapsing glomerulopathy (183 +/- 31 micromol/L) compared with those with FSGS (115 +/- 18 micromol/L), but the difference was not significant (P = 0.0504). The difference in proteinuria was not significant (P = 0.7668); it was 5.83 +/- 0.74 g/d in patients with collapsing glomerulopathy and 5.42 +/- 0.84 g/d in those with focal sclerosing glomerulonephritis. The difference in systolic (P = 0.4) and diastolic blood pressure (P = 0.556) was also not significant. Survival of the patients with collapsing glomerulopathy was worse than that of patients with FSGS (P = 0.025). Renal function survived 5 years in 40% of the patients with FSGS, but patients with collapsing glomerulopathy had no renal function survival. Our data suggest that idiopathic collapsing glomerulopathy is a distinct clinicopathologic entity with similar clinical features to focal sclerosing glomerulonephritis, but a worse prognosis and a rapidly progressive course toward end-stage renal disease. Comments: Comment in: Am J Kidney Dis 1999 Apr;33(4):801-3 |
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Hailemariam S, Walder M, Burger HR, Cathomas G, Mihatsch
M, Binswanger U, Ambuhl PM. Renal pathology and premortem
clinical presentation of Caucasian patients with AIDS: an
autopsy study from the era prior to antiretroviral therapy.
Swiss Med Wkly 2001 Jul 14;131(27-28):412-7. PRINCIPLES: Renal disease in patients with HIV infection is becoming increasingly frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found in patients of predominantly African-American and Hispanic origin. However, only limited data are available on renal pathology and premortem clinical presentation of kidney disease in Caucasian patients with AIDS. METHODS: To determine the prevalence, clinical presentation and aetiology of renal disease in Caucasian patients with AIDS at the time of death we have performed a prospective autopsy study with 239 patients who died of AIDS between 1981 and 1989. None of these patients had received HIV-specific antiretroviral therapy. Autopsies and histological analyses were performed on the basis of a standardised protocol. Clinical and laboratory data were gathered according to a uniform questionnaire. RESULTS: 95% of patients were of Caucasian race. 75% of all patients had extended AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36% of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and renal insufficiency (11%). Histopathological lesions were present in 43% of the autopsies, with two or more distinct structural lesions in 12.5% of patients. Of the pathological findings 28% were glomerular or vascular, 33% were non-glomerular, and 29% were combined lesions. The remaining 10% were renal infiltrations of infectious agents or neoplastic tissue. The most common findings were ischaemic changes and vascular scars (18% of patients), as well as pyelo- and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7% of patients, and only a single African patient had classical HIVAN. CONCLUSIONS: Renal involvement in HIV disease is very common at the time of death among patients of Caucasian origin. However, classical HIV-associated nephropathy is absent in this population. These findings suggest that kidney disease affects all races and supports the hypothesis that HIVAN is specifically related to non-Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific antiretroviral therapy. |
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Laurinavicius A, Rennke HG. Collapsing glomerulopathy--a
new pattern of renal injury. Semin Diagn Pathol 2002
Aug;19(3):106-15 Collapsing glomerulopathy is a pattern of renal injury that has emerged along with the epidemic of HIV infection. The disease process is now increasingly recognized in non-HIV patients. In HIV and non-HIV patients the disease shares many clinical and pathologic features, and, we presume, pathogenetic factors. The disease entity is characterized by very heavy proteinuria frequently combined with rapidly progressive renal failure, poor outcome, glomerular collapse with hyperplasia and other degenerative changes of the visceral epithelial cells, and prominent tubulointerstitial injury with frequent microcystic changes. HIV-associated nephropathy has a higher prevalence in blacks, high frequency of intra-endothelial tubuloreticular inclusions, and prominent microcystic tubular changes. These differences, however, are not sufficient to predict the patient's HIV status from the biopsy findings alone. Collapsing glomerulopathy can also develop in association with lymphoproliferative disorders, systemic lupus erythematosus-like and other autoimmune diseases, other immune deficiency syndromes and viral infections, and in the context of immunosuppressive therapy. |
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Nadasdy T, Allen C, Zand MS. Zonal distribution of glomerular collapse in renal allografts: possible role of vascular changes. Hum Pathol 2002 Apr;33(4):437-41. Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA. Collapsing glomerulopathy (CG), an aggressive variant of focal segmental glomerular sclerosis, is a renal disease with severe proteinuria and rapidly progressive renal failure. The pathogenesis of CG is unknown. It strongly resembles human immunodeficiency virus (HIV)-associated nephropathy, but the patients are HIV negative. The characteristic glomerular lesion is capillary loop collapse with prominent podocytes filling Bowman's space. Interestingly, these glomerular changes are usually associated with severe tubulointerstitial injury, including tubular epithelial degenerative changes, microcystic dilation of several tubules, and interstitial inflammatory cell infiltrate. Recently, it became evident that the morphologic pattern of CG may appear not only in native kidneys, but also de novo in renal allografts, and that the pattern of CG in renal transplants is not always associated with severe proteinuria. Studies describing CG in renal allografts are all based on biopsies. We report 3 allograft nephrectomy specimens that showed a zonal distribution of the characteristic collapsing glomerular changes with associated tubulointerstitial injury. All 3 kidneys had obliterative vascular changes. One nephrectomy specimen had chronic obliterative transplant arteriopathy, 1 had acute vascular rejection, and 1 had thrombotic microangiopathy. None of the patients had severe proteinuria. Our cases suggest that the morphologic pattern of CG in renal allografts may not represent the same disease process as CG in native kidneys and provide further evidence that collapsing glomerular changes do not define the disease entity of CG, but rather represent a pattern of renal injury. Among other factors, hemodynamic disturbance may play a role in the development of the pattern of CG in renal allografts. Copyright 2002, Elsevier Science (USA). All rights reserved.
Avila-Casado MC. [Collapsing glomerulopathy: a new entity associated with nephrotic syndrome and end-stage renal failure] Rev Invest Clin 1999 Nov-Dec;51(6):367-73 [Article in Spanish] Departamento de Patologia, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico, D.F. Collapsing glomerulopathy is an aggressive form of glomerular disease defined for its histopathological features of glomerular collapse, visceral epithelial cell damage and tubulointerstitial changes that are characteristic. Patients with collapsing glomerulopathy present with severe nephrotic syndrome, marked proteinuria, generally more than 10 g/day and rapid progression to chronic renal failure, or death due to complications of nephrotic syndrome, despite any form of treatment. Collapsing glomerulopathy presents as de novo or recurrent disease in the renal allograft. There is slight predominance in males and strong predominance in blacks as renal diseases in general. Collapsing glomerulopathy shares several clinical and histopathological features with focal and segmental glomerulosclerosis and HIV-nephropathy; nevertheless, there is enough evidence to support collapsing glomerulopathy as a different entity. It must be mentioned that collapsing glomerulopathy, focal and segmental glomerulosclerosis and HIV-nephropathy may have a similar pathophysiological mechanism of damage to the visceral epithelial cell.
Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999 Dec;56(6):2203-13 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. alaurinavi@ip.it Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. BACKGROUND: Collapsing glomerulopathy (CG) is a pattern of renal injury that is seen in association with HIV infection and that is increasingly recognized in non-HIV patients. METHODS: A review of native kidney biopsies with CG that were diagnosed between 1979 and 1997 in 18 HIV and 42 non-HIV patients is provided. RESULTS: HIV and non-HIV patients with CG were similar in terms of age, sex ratio, serum creatinine, proteinuria, the extent of collapsing and sclerosing glomerular lesions, and interstitial damage. A slight female predominance was found in both groups. In contrast to non-HIV patients, the HIV group was characterized by a high prevalence of blacks (94 vs. 57%), frequent tubuloreticular inclusions (76 vs. 29%), and microcystic tubular changes (72 vs. 40%). In 13 non-HIV patients, CG was associated with a systemic lupus erythematosus (SLE)-like disease (5), hepatitis C virus (HCV) infection (3), HTLV-I infection, MCTD, acute monoblastic leukemia, multiple myeloma, and cerebral arteritis. Overall, the renal survival of human immunodeficiency virus (HIV) and non-HIV patients with CG was not significantly different. Cox regression revealed that HIV infection had an adverse effect on short-term renal survival, with other significant risk factors being extensive interstitial fibrosis, high serum creatinine, proteinuria, and a low percentage of glomeruli with collapse. The slope of reciprocal creatinine was best predicted by the degree of proteinuria. Serum creatinine correlated with the extent of interstitial fibrosis, the male gender, and the percentage of glomeruli with collapse. Proteinuria was best predicted by the extent of effacement of podocyte foot processes. CONCLUSIONS: CG shares many clinicopathological similarities in HIV and non-HIV patients. In some non-HIV patients, CG was associated with autoimmune diseases, lymphoproliferative disorders, and viral infections.
Kihara I, Yaoita E, Kawasaki K, Yamamoto T, Hara M, Yanagihara T. Origin of hyperplastic epithelial cells in idiopathic collapsing glomerulopathy. Histopathology 1999 Jun;34(6):537-47 Department of Pathology, Institute of Nephrology, Niigata University School of Medicine, Niigata, Japan. AIMS: Glomerular epithelial cell hypertrophy and hyperplasia are listed as the primary criteria for the diagnosis of collapsing glomerulopathy (CG), a distinct variant of focal segmental glomerulosclerosis. However, the extent of podocyte phenotypic alterations that occur in CG, and the origin of the hyperplastic epithelial cells remain to be established. METHODS AND RESULTS: Renal biopsy materials from seven out of three patients with CG were studied by serial section analysis for immunohistochemistry and electron microscopy. Markers for podocytes (PHM5 and synaptopodin), parietal epithelial cells (PECs: cytokeratin) and macrophages (CD68) were used for the immunohistochemistry. Multiple ultrathin sections from a total of 15 glomeruli, including some from patients with CG, were examined by electron microscopy. Glomerular adhesions occurred in 71% of the serially sectioned glomeruli taken from patients with CG. Hyperplastic epithelial cells were immunonegative for podocyte markers and CD68, but invariably immunopositive for cytokeratin. Electron microscopy revealed that detachment of the podocytes from involved glomerular capillary walls was extensive. Many of the detached podocytes appeared to be necrotic and apoptotic. In contrast, junctional complexes of desmosomes and zonula adherens connected hyperplastic epithelial cells to each other. Cilia were also often observed. CONCLUSIONS: The results of our ultrastructural and immunohistochemical study suggest that the hyperplastic epithelial cells observed in cases of CG are derived from PECs. Our results raise the possibility that PECs play a general role in covering glomerular tufts from which the podocytes have disappeared.
Meyrier A: E pluribus unum: The riddle of focal segmental glomerulosclerosis. Semin Nephrol 2003 Mar;23(2):135-40. Semin Nephrol. 2003 Mar;23(2):135-40. Related Articles, Links E pluribus unum: The riddle of focal segmental glomerulosclerosis. Hopital Europeen Georges Pompidou, and INSERM U 430, Paris, France. A recent consensus conference proposed a new classification for focal segmental glomerulosclerosis (FSGS). Five patterns have been defined: FSGS not otherwise specified, perihilar variant, cellular variant, tip variant, and collapsing variant. In light of the multiplicity of classification schemes in use, the promise of a rational and uniform scheme for FSGS pathology is most welcome. This approach has worked extremely well for the classification of lupus nephritis. It does not necessarily mean, however, that this new classification scheme will help to select treatment protocols according to histopathologic subsets of FSGS. In fact, one renal biopsy examination may show multiple variants and this classification, despite many merits, still lumps categories that should be split and splits categories that should be lumped together. It has become clear that despite its histologic diversity FSGS begins as a podocyte disease that progresses from a cellular to a scar lesion. Recent years have brought about astonishing insight into the complex molecular array of proteins forming the slit diaphragm between podocyte foot processes, a narrow space essential for restricting glomerular permeability to albumin. Concentrating on the podocyte rather than on the glomerular tuft is helpful for abolishing the classic distinction between primary versus secondary forms of FSGS, a distinction that crumbles away with each new evidence of genetic, ischemic, or viral etiologies of FSGS, despite similar lesions. In fact, recent studies focusing on the podocyte changes that occur in various subsets of FSGS have unraveled the striking phenomena of podocyte dedifferentiation and transdifferentiation along with differential expression of cyclin-dependent kinase inhibitors. Interestingly, the latter showed that expression of cyclin-dependent kinase inhibitors p21 and proliferation marker Ki-67 are the same in cellular FSGS, collapsing glomerulopathy, and human immunodeficiency virus-associated FSGS. Taken together these findings lead to a reassuring unitary interpretation of the pluralistic appearance of FSGS by histopathology. Clearly, further studies of the podocyte will lead to improved understanding of FSGS and to improved classification schemes that are grounded in molecular understanding of glomerular injury and that will guide the clinician in the choice of treatment and prognosis. Copyright 2003 Elsevier Inc. All rights reserved. Meehan SM, Pascual M, Williams WW, Tolkoff-Rubin N, Delmonico FL, Cosimi AB, Colvin RB. De novo collapsing glomerulopathy in renal allografts. Transplantation 1998 May 15;65(9):1192-7 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA. BACKGROUND: Collapsing glomerulopathy is a recently described form of glomerular injury characterized by capillary collapse and visceral epithelial hypercellularity associated with nephrotic range proteinuria and a rapid, progressive decline in renal function. The lesion has rarely been described in allografts. METHODS: We reviewed 892 allograft biopsies from a population of 1079 recipients who received renal transplants between 1978 and 1996. RESULTS: Five cases of de novo collapsing glomerulopathy were identified (0.6% of biopsies; 3.2% since 1993). None occurred before 1993. The patients were 31 to 66 years of age and they presented 6 to 25 months after transplantation. The 24-hr urinary protein ranged from 1.8 to 11.8 g. All patients and donors were negative for the human immunodeficiency virus and had no risk factors for human immunodeficiency virus infection. Diffuse or focal, global or segmental collapse of glomerular capillaries, swelling and hypercellularity of the visceral epithelium, hyaline arteriolosclerosis, and interstitial fibrosis were characteristic histologic features. Two cases had concomitant glomerular immune complex deposits. Progressive decline in allograft function occurred within 2-24 months after diagnosis, culminating in return to dialysis in all patients. CONCLUSION: Collapsing glomerulopathy can arise in renal allografts as a de novo disease. Although its pathogenesis remains to be clarified, it is important to distinguish this lesion in allografts as it can be associated with rapidly progressive graft failure.
Bariety J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A. Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 1998 Apr;53(4):918-25 Service de Nephrologie and INSERM U 430, Hopital Broussais, Paris, France. Collapsing glomerulopathy (CG), a severe form of focal segmental glomerulosclerosis (FSG), is characterized by tuft retraction and consolidation in numerous glomeruli and changes in podocyte morphology and topography. Other glomeruli are less affected. Collapsing glomerulopathy is also characterized by tubulointerstitial atrophy and fibrosis. The pathophysiology of the glomerular and tubulointerstitial lesions is poorly understood. We studied renal tissue of five Black and three White patients, all human immuno-deficiency virus (HIV) negative, with nephrotic syndrome, renal failure, and histological evidence of CG. Immunohistochemistry identified normal podocyte phenotypes by podocalyxin, vimentin and complement receptor 1 (CR1) labeling. Three monoclonal antibodies were used to further characterize podocyte epitopes: anti-CD68 clone KP1, anti-CD68 clone PG-M1 and anti-M130 clone M18 (Ber-MAC3). Light microscopy of collapsed glomeruli showed podocyte swelling, vacuolization, multinucleation, "cobblestone-like" alignment around the glomerular tuft, and pseudo-crescent formation in Bowman's space. In collapsed glomeruli, podocalyxin, vimentin and CR1 labeling tagged both normal and vacuolated podocytes still attached to the GBM, but labeling was not found in cobblestone-like podocytes or in podocytes detached from the GBM. Conversely, numerous podocytes undergoing detachment and shedding into Bowman's space expressed macrophagic-associated epitopes. Cells with macrophagic-associated epitopes clumped in cystically dilated tubules and were aligned in tubules of smaller caliber. Their appearance was that of viable cells. There was no morphologic indication that these cells expressing macrophage-associated antigens originated from outside the glomeruli or outside the tubules. We conclude that in CG podocytes detach from the GBM, lose their normal podocytic phenotype and acquire macrophage differentiation antigens. The presence of cells with such antigens in tubular lumens suggests that detached metaplastic podocytes progress along the tubule or, alternatively, that CG tubular cells also undergo metaplastic changes into macrophage-like cells. |
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